Spironolactone may save the day with resistant hypertension
Source: Engbaek M, et al. The effect of low-dose spironolactone on resistant hypertension. J Am Soc Hypertens 2010;4:290-294.
Although the definition of resistant hypertension (r-HTN) has some variation, in the United States it is most commonly defined as inability to achieve target blood pressure with optimized doses of three antihypertensive agents, including a diuretic. Depending upon the population studied, as many as 15%-18% of subjects entering clinical trials who presumably receive some of the best care medicine has to offer are ultimately determined to have r-HTN.
Spironolactone (SPIR) is an aldosterone antagonist with modest diuretic activity. It has been shown to be effective in reducing blood pressure independent of aldosterone status; that is, one does not have to be a "high aldosterone" subject to enjoy meaningful BP reduction.
Engbaek et al report on 344 r-HTN subjects (mean BP 169/88, while already on three other medication), who were treated with SPIR 25 mg or 50 mg QD. They found a prompt and sustained mean BP reduction with SPIR: a 17/7 mm Hg reduction at 1 month, 24/10 mm Hg reduction at 3 months, and 26/11 mm Hg reduction at 6 months, all of which were statistically significant. The two most predictable adverse effects of SPIR, hyperkalemia and gynecomastia, were infrequent: 4.1% and 5.2%, respectively. Other clinical trials corroborate the utility and tolerability of SPIR to manage r-HTN. Clinicians should be reassured that < 10% of participants discontinued SPIR secondary to adverse events.
Fish oils: Where's the beef?
Source: Kromhout D, et al. n-3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med 2010;363:2015-2026.
Observational data indicate that populations with high intake of fish oil have less cardiovascular disease (CVD) endpoints, spurring clinical trials to elucidate the relationship. A 2008 meta-analysis suggested that in persons with existing coronary heart disease (CHD), supplements of fish oils (n-3-fatty acids, e.g., eicosapentaenoic acid and docosahexaenoic acid) reduced CHD mortality by as much as 20%. This beneficial effect has been attributed to a reduced vulnerability to arrhythmia provided by fish oils; disappointingly, the inclusion of fish oil supplements in study subjects with implantable cardioverter-defibrillators did not confirm an anti-arrhythmic effect.
To clarify the potential role of fish oil supplementation for CHD patients, the Alpha Omega Trial enrolled men and women age 60-80 with a history of myocardial infarction (n = 4837). Study subjects were randomized to fish oil supplementation or placebo for 40 months.
Fish oil supplementation did not provide a statistically significant reduction in CVD events. Because many of the study subjects were receiving other interventions to reduce CVD risk (e.g., statins, antiplatelet agents, BP drugs), the authors posit that it is possible that these results, which are divergent from earlier trials, reflect the lesser available margin for improvement in persons already receiving other good tools for CVD risk reduction.
Gait speed and survival in older adults
Source: Studenski S, et al. Gait speed and survival in older adults. JAMA 2011;305:50-58.
The frailty of senior citizens is often portrayed on-stage by slow, stiff gait. This representation may be much more than theatre. Indeed, according to this pooled analysis of a very large data set (34,485 community-dwelling senior citizens), gait speed is linearly associated with mortality among persons age 65 years and older.
Gait speed in the studies was calculated by timing the study subjects while they walked distances varying from 2.4 to 6 meters by simply dividing the distance covered by elapsed time, recorded as meters/second. After obtaining baseline gait speed, study subjects were followed for 6-21 years.
For each 0.1 meter/second increase in baseline gait speed, there was a 12% higher rate of survival. This was independent of gender, BMI, smoking, blood pressure, or self-reported health.
Should clinicians wish to consider using gait speed as a health predictor, the method is simple: The patient is asked to walk over a predetermined distance with the instructions "Walk at your usual pace, as if you were walking down the street." No particular encouragement or stimulus to promote intensification of effort is necessary.
Rifaximin for IBS without constipation
Source: Pimentel M, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med 2011;364:22-32.
It has been recognized for more than a decade that most patients with IBS have abnormal lactulose hydrogen breath tests results, consistent with small bowel bacterial overgrowth. Neomycin treatment, which can re-establish bowel flora, has shown modest efficacy in IBS, but is limited by tolerability issues. Other systemic antibiotics have not provided consistent symptomatic improvement in IBS. A previous pilot trial of rifaximin found that 10 days of treatment provided symptomatic improvement as measured 10 weeks later.
The TARGET trials are two identical double-blind, placebo-controlled trials of subjects with IBS without constipation. Patients were randomly assigned to rifaximin 550 TID or placebo for 2 weeks. Symptoms were monitored for up to 10 weeks. The primary outcome was the proportion of individuals reporting adequate relief of global IBS symptoms. The main secondary outcome was relief of bloating. Additional outcomes included abdominal pain and stool consistency.
Rifaximin provided a statistically significant improvement in global symptoms, bloating, abdominal pain, and stool consistency. Consonant with a very favorable tolerability profile seen in prior clinical trials, the safety profile of rifaximin was similar to placebo in this report. It is anticipated that systemic effects of rifaximin will be rare, since only a miniscule proportion of administered drug enters the systemic circulation.
Short-term treatment with rifaximin can provide statistically significant improvements for patients with IBS without constipation.
Pre-exposure HIV prophylaxis for men who have sex with men
Source: Grant RM, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010;363:2587-2599.
Men who have sex with men (msm) are a high-risk group for acquisition of HIV, but other than safe sex practices, there has been little encouraging information about chemoprophylaxis. Certainly clinicians have some degree of confidence in the efficacy of post-exposure HIV prophylaxis post-needle stick in the health care setting, but the only population in which pre-exposure prophylaxis has been studied utilized tenofovir vaginal gel in women in Africa, reporting a 39% reduction in HIV infection.
HIV-seronegative men (or transgender women) who have sex with men (n = 2499) were randomized to a combination antiretroviral treatment (emtricitabine and tenofovir) or placebo once daily. They were followed for up to 2.8 years (median 1.2 years).
During follow-up, all subjects were seen every 4 weeks, during which they were counseled on safe sex practices, sexually transmitted diseases (STDs), and STD risk reduction.
At the conclusion of the trial, 36 of 1224 pre-exposure prophylaxis patients sero-converted vs 64 of 1217 placebo subjects (a 44% reduction in HIV incidence). Tolerability of the active antiviral treatment was excellent. The risk reduction demonstrated in this trial seems all the more remarkable because the reduction in unsafe sex practices attributed to the repetitive sexual health education and counseling during the trial would tend to minimize benefits of the medication.
Treating venous thromboembolism with rivaroxaban
Source: The EINSTEIN Investigators. Oral rivaroxaban for symptomatic venous thromboembolism. N Engl J Med 2010;363:2499-2510.
The treatment of acute venous thromboembolism commonly is managed successfully with enoxaparin followed by intermediate to long-term prevention of recurrent thromboembolism with warfarin.
Despite a proven track record of efficacy, warfarin has limitations, including the need for ongoing monitoring, problematic interactions with medications and food, and risk of significant bleeding, which occurs in 1%-2% of patients using long-term warfarin.
Rivaroxaban is a direct factor X inhibitor administered orally once daily. It is effective both acutely (hence, it may be utilized instead of heparin during the acute phase of venous thromboembolism) and chronically. Because it does not have any interactions with food and does not require monitoring, it provides many fewer obstacles to successful patient management than warfarin or heparin-warfarin combinations.
The EINSTEIN Investigators reported on two trials: One compared rivaroxaban with enoxaparin + warfarin for acute venous thromboembolism (n = 3449), and the other compared rivaroxaban with placebo in subjects who had completed 6 months of warfarin treatment for DVT.
For acute venous thromboembolism, rivaroxaban was non-inferior to enoxaparin + warfarin. In the long-term trial, rivaroxaban was superior to placebo. Rivaroxaban appears to provide an attractive alternative treatment for venous thromboembolism.
Spironolactone may save the day with resistant hypertension, Fish oils: Where's the beef?, Gait speed and survival in older adults, Rifaximin for IBS without constipation, Pre-exposure HIV prophylaxis for men who have sex with men, Treating venous thromboembolism with rivaroxaban,You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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